Synthesis Of Porphyrin (or Chlorin) Isopropyl -5- Fluorouracil -1-yl Acetate

As a kind of antitumor drug,5-Fluorouracil has inhibition effect on many kinds of cancer, but its defect is that it also seriously hurts the normal cells while it kills the cancer cells. 5-Fluorouracil's bioavailbility is very low, oral absorption is not completely and the half life time is shot. These shortcomings limit its application of clinic. In recent years,many chemists have modified their chemical structures and hope to develop a better drug to overecome its shortcomings.Phtodynamic therapy has caused great interests of chemists, medicals and biologists. Chlorins, as the second photosensitizer,is superior to porphyrins in the following aspects: enchanced absorption in far infrared region,increased therapy depth,less dosage,shorter retaining time and smaller toxic effects.In order to improve the lipophilicity and half life time of 5-Fu, we synthesize 5-Fluorouracil-1-acetic isopropyl esters.We will synthesize"porphyrin(chlorine)-5- Fluorouracil-1-acetic isopropyl esters"which has dual functions of anti-cancer drugs and photosensitizers.In this paper,we synthesis and charactered seven porphyrin-5-Fu-1-acetic isopropyl ethers, seven novel manganese porphyrin-5-Fu-1-acetic isopropyl ethers and four chlorine-5-Fu-1- acetic isopropyl ethers.These results are as follows:In the first part, seven novel porphyrin-5-Fu-1-acetic isopropyl ether complexes have been characterized by UV,IR,1HNMRand MS spectra. Seven novel manganese porphyrin -5-Fu-1-acetic isopropyl ether complexes have been characterized by UV-Vis and IR spectra.In the second part,four chlorine-5-Fu-1-acetic isopropyl ethers have been characterized by UV,IR,¹HNMR(except of D₄) and MS spectra.In the third part, optimum reaction and separaion conditions have been reaserched and improved.